Data from our studies clarify the substrates of brain dysfunction in cretinism and the role of hormones in normal brain function particularly during critical periods of brain growth and development. Thus, our research deals with important basic questions in the area of normal behavior, neuroendocrine relationships, and neural development and their various modifiers. To establish a more basic understanding of underlying mechanisms of thyroid hormone action, we are not entering into studies on the metabolism of thyroid hormones and the effects of thyroid hormone metabolities on receptors in vivo and in vitro at different subcellular levels. In our thyroid receptor studies we will compare mitochondrial receptors with nuclear and with cytoplasmic receptors at different ages in the brain and liver. The in vitro work on neuroblastoma and glioma cells will utilize the hypothyroid vs. euthyroid state to compare changes in thyroid receptor kinetics with altered biochemical and morphological parameters. The investigation into the relationship between thyroid hormones and neurotransmitters will be continued by focusing on specific receptors (e.g., dopamine) and neurotransmitter turnover. The functional consequences of altered thyroid hormone state will be correlated with the development of sleep patterns in the rat.